For a deeper investigation of the potential mechanisms affecting the survival difference, we first compared the genes with high-frequency rates of somatic mutations in lung cancers, such as TP53, TTN, and MUC16. The results showed that the mutation rates of TP53 and TTN were highly associated with the risk scores predicted by the prognostic signature, which may be one of the reasons for the poorer prognosis of LUAD patients in the high-risk group. Here, TP53 is linked to lung cancer.